Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

Phase 1

Completed

Conditions: Chronic Kidney Disease

Interventions: Drug: D6-25-hydroxyvitamin D3

Registration Number: NCT03576716

Lead Sponsor: University of Washington

Brief Summary: The goal of this study is to determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach.

Detailed Description: We expect that this study will enhance interpretation of available diagnostic tests, inform the results of ongoing large clinical trials of vitamin D supplements, and help develop new strategies to target vitamin D to improve health.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Successful prior completion of related protocol CLEAR (NCT02937350) or CLEAR-CF (NCT03104855)
Age ≥ 18 years
Self-reported race Caucasian, African American, or African

Exclusion Criteria

Primary hyperparathyroidism
Gastric bypass
Tuberculosis or sarcoidosis
Current pregnancy
Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin >=2 mg/dL, serum albumin <=3.5 g/dL, or PT >= 4 seconds)
History of kidney transplantation (unless failed transplant now treated with hemodialysis)
Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed)
Serum calcium > 10.1 mg/dL
Hemoglobin < 10 g/dL

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study Population	D6-25-hydroxyvitamin D3	D6-25-hydroxyvitamin D3 with vitamin D3

Primary Outcome Measures

Name	Time	Method
Change in Metabolic Clearance of D6-25(OH)D3	Baseline, 6 months	Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Secondary Outcome Measures

Name	Time	Method
Change in AUC of D6-25(OH)D3	Baseline, 6 months	AUC is calculated using the linear trapezoidal method. Change in the AUC of D6-25(OH)D3 will be calculated as D6-25(OH)D3 AUC measured during CLEAR-PLUS minus D6-25(OH)D3 AUC previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.
Change in Terminal Half-life of D6-25(OH)D3	Baseline, 6 months	Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations. Change in the terminal half-life of D6-25(OH)D3 will be calculated as D6-25(OH)D3 half-life measured during CLEAR-PLUS minus D6-25(OH)D3 half-life previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.
Change in Volume of Distribution of D6-25(OH)D3	Baseline, 6 months	Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma. Change in the volume of distribution of D6-25(OH)D3 will be calculated as D6-25(OH)D3 volume of distribution measured during CLEAR-PLUS minus D6-25(OH)D3 volume of distribution previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.